Disentangling comorbidity: symptom dimensions of internalizing and functional disorders in a large general population sample.
Saini, Urvi, Aggen, Steven H, Oldehinkel, Albertine J et al. · BMC psychiatry · 2026 · DOI
Quick Summary
This study looked at how symptoms of depression, anxiety, ME/CFS, fibromyalgia, and irritable bowel syndrome overlap in over 100,000 people. Researchers found that these conditions share common symptoms like fatigue, sleep problems, and difficulty concentrating—which they call 'general malaise'—rather than being completely separate diseases. Understanding these shared symptoms may help explain why people often have multiple conditions at the same time.
Why It Matters
This research provides evidence that ME/CFS shares a common symptom structure with other conditions rather than being entirely distinct, which could explain why ME/CFS patients often experience comorbid psychiatric and functional symptoms. Identifying the 'general malaise' dimension as central to multiple disorders offers a new framework for understanding and potentially treating the overlapping symptoms that burden ME/CFS patients. The finding that chronic stress associates with all symptom dimensions highlights a potential intervention target across conditions.
Observed Findings
Five symptom dimensions were identified: depression, anxiety, IBS, musculoskeletal pain, and general malaise.
ME/CFS and fibromyalgia symptoms loaded onto musculoskeletal pain and general malaise dimensions rather than forming separate diagnostic dimensions.
The general malaise dimension captured transdiagnostic symptoms (fatigue, unrefreshing sleep, concentration difficulty) present across multiple conditions.
The general malaise dimension was correlated with all other symptom dimensions (except IBS) and associated with all five disorders.
Chronic stress was the only risk factor significantly associated with all five symptom dimensions.
Inferred Conclusions
Internalizing and functional disorders share a common transdiagnostic symptom structure centered on general malaise rather than being entirely separate entities.
The general malaise dimension may be central to understanding comorbidity across psychiatric and functional disorders and warrants investigation as a treatment target.
ME/CFS and fibromyalgia symptoms are not sufficiently distinct to form independent diagnostic dimensions in the general population, suggesting substantial symptom overlap with other conditions.
Remaining Questions
Do the identified symptom dimensions replicate in clinically diagnosed ME/CFS patients, or do they differ from patterns in the general population?
What This Study Does Not Prove
This cross-sectional study cannot establish causality—it shows which symptoms cluster together but not whether one condition causes another or what temporal relationships exist. The study relies on self-reported symptoms without confirmed clinical diagnoses, so results may not apply to formally diagnosed ME/CFS patients. The findings describe symptom patterns in the general population and do not prove that the identified dimensions operate identically in clinical populations with diagnosed disease.